A Phase I Pharmacokinetic Study in HIV-Positive Subjects of Oral Ganciclovir and Concomitant Antiretroviral Zidovudine and Didanosine

Patients currently on either AZT or ddI receive ganciclovir therapy.

Inclusion criteria

Concurrent Medication:

Required:

• Concomitant AZT or ddI.

Allowed:

• Probenecid.
• Aerosolized pentamidine.

Patients must have:

• Asymptomatic HIV infection.
• CMV seropositivity or CMV culture positivity at present or at any time in the past.
• No history of CMV disease (e.g., retinitis, colitis) or any other AIDS-defining illness.
• Treatment with AZT or ddI for at least 1 month prior to study entry.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Uncontrolled diarrhea (three or more loose stools/day).
• Clinically significant gastrointestinal symptoms including persistent nausea or abdominal pain.
• AZT patients only:
• Deficiency in glucose-6-phosphate dehydrogenase.
• ddI patients only:
• Grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

• Combination antiretroviral therapy.
• G-CSF or GM-CSF.
• Acyclovir.
• Amphotericin B.
• Amikacin.
• Captopril.
• Carbamazepine.
• Cimetidine.
• Cyclosporine.
• Glutethimide.
• Gentamicin.
• Griseofulvin.
• Ibuprofen.
• Imipenem-Cilastatin.
• Lithium.
• Methicillin.
• Methotrexate.
• Naproxen.
• Pentamidine (Pentam 300) (Aerosolized drug permitted).
• Phenacetin.
• Phenobarbital.
• Phenytoin.
• Piroxicam.
• Ribavirin.
• Rifampin.
• Tobramycin.
• Vidarabine.
• Zalcitabine.
• Other investigational drugs.

Patients with the following prior conditions are excluded:

• History of hypersensitivity to acyclovir or ganciclovir.
• AZT patients only:
• History of gout, uric acid, kidney stones, peptic ulcer or porphyria.
• ddI patients only:
• History of pancreatitis or alcoholism, or seizures within 6 months prior to study entry or prior need for anticonvulsant therapy.

Prior Medication:

Excluded:

• Combination antiretroviral therapy within 1 month prior to study entry.

Required:

• AZT at 500 mg/day for at least 1 month prior to study entry (with 100 mg administered five times per day for at least 1 week prior to study entry). OR
• ddI at recommended dose for at least 1 month prior to study entry (with 250 mg administered every 12 hours for at least 1 week prior to study entry).

History of alcoholism (in ddI patients).